Vascular smooth muscle cell response to cyclic mechanical stretch and aortic dissection

  • Yoshizumi Masanori
    Department of Pharmacology, Nara Medical University School of Medicine
  • Zhao Jing
    Department of Pharmacology, Nara Medical University School of Medicine
  • Kyotani Yoji
    Department of Pharmacology, Nara Medical University School of Medicine

Bibliographic Information

Other Title
  • 伸展刺激に対する血管平滑筋細胞応答と大動脈解離予防の治療標的
  • シンテン シゲキ ニ タイスル ケッカン ヘイカツキン サイボウ オウトウ ト ダイドウミャク カイリ ヨボウ ノ チリョウ ヒョウテキ

Search this article


<p>Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC death, phenotypic switching, and migration, leading to aortic dissection. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) caused JNK- and p38-dependent cell death and that a calcium channel blocker, azelnidipine and an angiotensin II receptor antagonist, olmesartan decreased the phosphorylation of JNK and p38 and, subsequently, decreased cell death by CMS. JNK and p38 inhibitors also inhibited CMS-induced cell death. In addition, we showed that the expression of Cxcl1 and Cx3cl1 chemokines was induced by CMS in a JNK-dependent manner. Expression of Cxcl1 was also induced in VSMCs by hypertension produced by abdominal aortic constriction in mouse. In addition, antagonists against the receptors for CXCL1 and CX3CL1 increased cell death, indicating that CXCL1 and CX3CL1 protect RASMCs from CMS-induced cell death. We also revealed that STAT1 is activated in RASMCs subjected to CMS. Taken together, these results indicate that CMS of VSMCs induces inflammation-related gene expression, including that of CXCL1 and CX3CL1, and activates JNK and p38 MAP kinases, which may play important roles in the stress response against CMS caused by acute rise in blood pressure.</p>



See more

Details 詳細情報について

Report a problem

Back to top